We will develop analytic tools for the pharmacokinetic study of racemic anticoagulant drugs in human subjects with the synthesis of carbon-13 (stable isotope) labeled enantiomers, with their detection and quantitation in blood, urine, and stool by mass spectrometry. The direct study of the pharmacologic activity and metabolic disposition of racemic warfarin and racemic phenprocoumon will be undertaken by labelling each enantiomer with 13C-isotope and combining each 13C-labeled enantiomer with the opposite 12C-enantiomer. Each 13C-/12C-racemate will be administered to normal subjects, and both the hypoprothrombinemia and the metabolic fate of each enantiomer will be quantitated in blood, urine and stool. Some drug interactions with racemic mixtures are stereoselective. To determine the stereoselectivity of the interaction of warfarin with phenylbutazone, and barbiturates, the subjects will receive a single-dose or 21-day course of 13C-/12C-racemic warfarin with and without a course of the interacting drug. The quantitative data on the labelled racemates of warfarin and phenprocoumon and their metabolic products will be analyzed pharmacokinetically to compare the total metabolic disposition of these two racemic anticoagulants to determine whether therapy can be made safer and more stable by using only one of the enantiomorphs instead of the racemates for long-term anticoagulant therapy.